Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0476089 (endometrial cancer)
 11,379 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Since hormones relate to the etiology of breast cancer, 40 studies have looked at the possible association of oral contraceptives (OCs) with breast cancer. Most research conducted through 1986 and including the largest related case control study and several after 1986 found no association between ever use of OCs and breast cancer. On the other hand, some studies conducted after 1986 with women 45 years old who had breast cancer and had taken OCs have suggested a dose response relationship, 2 fold increased risk of breast cancer, or increased risk with duration of OC use. These results motivated several organizations to review the literature and to issue guidelines. The US Food and Drug Administration, the UK Committee on the Safety of Medicines, and IPPF did not find a reason to change practices. The Committee on the Safety of Medicines did suggest, however, that health providers mention the possible increase in risk. At least 8 studies have revealed an increased risk of cervical cancer with duration of OC use, especially after 5 years of use. Yet experience has disclosed an obstacle to understanding the relationship between cervical cancer and OC use--cervical cancer may be caused by the human papilloma virus transmitted by sexual intercourse. Unlike results of breast and cervical cancer research, research results have clearly established that OC use lowers the risk of endometrial cancer by about 50% and the risk of ovarian cancer by about 40%. In fact, the US Cancer and Steroid Hormone [CASH] study showed a protective effect of OCs for endometrial and ovarian cancers at least 15 years after discontinuation. Even though some studies found a dose response effect with duration of use, a large international study did not find any relationship between OC us and liver cancer. Moreover studies did not reveal an association between OC use and malignant melanoma or pituitary adenoma.
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PMID:Neoplastic effects of oral contraceptives. 167 77

Total Hysterectomy has been until non performed by extracervical "enucleation" of the fascia of the uterine corpus with amputation of the vagina. The new method leaves the extrafascial highly vascularised vascular stem, the corresponding nerves and the topography of the ureter untouched. It is limited to an intrafascial cylindriform enucleation of the cervix. The diameter of the cervical cylinder can be determined beforehand by vaginal sonography. Punching-out is effected from a new instrument C.U.R.T. (= calibrated uterine resection tool) of 10-20 mm diameter. A cervicohaemostaser provides for safe transvaginal haemostasis in the residual cervix. The transvaginal sexual sensations of the patient are not impaired due to the fact that the cardinal ligaments are preserved as well as the nerve supply of the cervical fascia. Suspension of the cervical fascia at the supporting ligaments of the uterus can be performed in an ideal manner. Pelviscopic extirpation of the uterus is done in the classical way used in abdominal hysterectomy with ligature and suture. Morcellated cylinders of 2-3 cms in diameter, of the cervix and corpus uteri and even of myomas up to the size of a child's head, will suffice for relevant histological examination. The physical stress to which the patient is exposed is about the same as in routine surgical pelviscopy. The abdominal space remains practically unopened in pelviscopic transabdominal hysterectomy. Pelviscopic transabdominal hysterectomy with and without adnexae according to the CASH technique corresponds to surgery performed with a minimum of invasiveness. It is fully sufficient as regards cancer prophylaxis with respect to cervical or endometrial cancer.
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PMID:[Hysterectomy via laparotomy or pelviscopy. A new CASH method without colpotomy]. 183 98

The evidence of the effects of combined oral contraceptives (COCs) on mortality and morbidity is reviewed. All the 11 case-control studies published since 1980 reported and approximate halving of endometrial cancer risk among COC users. The CASH study showed that the protective effect was apparent after 12 months' use, and users had 40% of the risk of non-users after 2 years' use. A study showed that 5 patterns of self-perceived prolonged, heavy, frequent, irregular, or painful bleeding during menstruation were reported less frequently in COC users than in users of other methods. Benign breast disease is rarer, and functional ovarian cysts are less frequent in COC users. Lower-dose preparations may carry a lower risk of myocardial infarction. Smoking possibly potentiates the risk associated with oral contraceptive (OC) use, and it is a major risk factor for myocardial infarction. The Oxford/FPA study found a 2-3-fold increase in incidence of non-haemorrhagic stroke among current OC users. The epidemiologic data on the current risk of venous thromboembolism in relation to OC use are equivocal. New lower dose COCs have a smaller adverse effect on the lipid profile: they cause a smaller increase in low density lipoprotein cholesterol (LDL) and a variable but smaller decrease in high density lipoprotein cholesterol (HDL). The large CASH study, based on 2088 cases, found a significantly elevated relative risk (2.7) of breast cancer, but only in women who had used the OC for at least 11 years. Of 6 case-control studies of hepatocellular carcinoma and OC use published since 1983, all but one showed a large elevated relative risk of around 4-fold. Delayed return of fertility has been observed in nulliparous women 30 who had 2 years; continuous exposure to COCs, although this may not be associated with low-dose, modern OCs. Malignant melanoma, pituitary adenoma, gallbladder disease, and chronic inflammatory bowel disease have been possibly associated with adverse side effects, but results are so far inconclusive.
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PMID:Combined oral contraceptives: risks and benefits. 832 3

Findings of several recent epidemiological studies of the relationship between oral contraceptives (OC) and the development of cancer were summarized. Enough time has now elapsed since the introduction of OCs to enable investigators to examine the latent and longterm effects of OC use on the development of cancer. In general recent findings indicated that OC use was not associated with the development of breast cancer breast cancer and was negatively associated with endometrial ovarian cancer. Findings in regard to cervical and liver cancer cases and melanoma were unclear. In reference to breast cancer, in a study of 1191 breast cancer cases and 5026 controls, conduct Rosenberg and others, the relative risk of breast cancer for women who ever used OCs as compared with women who never used OC was 1.0. No increased risk was observes for women who 1) used OCs for more than 5 years, even 10 years following OC discontinuance; 2) took OCs while they were nulliparous or premenopausal; 3) had a family history of benign or 1st degree breast cancer. 4735 breast cancer patients and 4685 controls were included in the recent Cancer and Steroid Hormone Study (cash) conducted by the Centers for Disease Control. Results indicated that the relative risk of breast cancer for every users of OCs compared to never users was 0.9. No increased risk was observed for women who took OCs for 10 or more or 20 or more years. No increased risk was associated with any of the OC formulations commonly available in the US. The cash data were also used to assess issues raised in 2 other studies. A Los Angeles study of 314 cases and 314 controls found that women who used high progestin OCs for 2 or more years had s significantly increased risk of developing breast cancer by age 37, and a Britidh study found that OC use of 4 or more years prior ro 1st pregnancy was associated with an increase risk of cancer by age 45. In terms of the cash data no increased risk of breast cancer by the ages specified above was observed for these 2 identically defined subgroups of OC users. Several studies found that the risk of developing ovarian cancer was reduced by 50% for OC users. Furthermore, the risk decreased as duration of OC use increased, and the protevtive effect continued for at least 10 years following discontinuation of OC use. An initial analysis of CASH data revealed that the reduced risk was associated with all types of OC formulations currently marketed in the US. Several studies found a similar reduction in the risk of endometrial cancer among OC users. According to the CASH data, the relative risk of endometrial cancer was 0.5 for women who used OC for 12 or more months compared to never users, the protective effect lasted for at least 10 years, and the reduced risk was observed for the 7 most common OCs used in US. Most studies which included OC users detected a positive relattionship between OC use and the development of cervical neoplasms however, the data in these studies is subject to selective and misclassification biases and confounding effects. Despite these problems, there is a possibility that OC use enhances the risk of cevical neoplasms and speeds up the transition from cervical dyplasia to invasive cancer. The results of studies. Taking into account the role of sun exposure, need to be undertaken. The relationship between OC use and liver tumors has not be examined epidemiologically, and this deficit should be corrected.
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PMID:Researchers can now investigate long-term effects of OCs on cancer. 1227 18

Human endometrial epithelial cells undergo apoptosis immediately before the menstrual period. Apoptotic signalling was analysed using human endometrial tissue and a human endometrial carcinoma cell line (HHUA). Activity levels of caspase-3, -8, and -9 were elevated in human endometrium during the late secretory phase and in HHUA cells incubated with an anti-Fas monoclonal antibody (mAb). Fas-mediated apoptosis of HHUA cells was blocked by prior exposure to inhibitors of caspase-9, -8 and -3. In HHUA cells treated with anti-Fas mAb, a release of cytochrome c was detected in the cytosolic fraction, in addition a full-length Bid was degraded. Full-length FLIP(L) (p55) was degraded during apoptosis, and p29 (regarded as the product of p55 cleavage) appeared instead of FLIP(L). In normal human endometrial tissue, Bid degradation was also observed in a cyclic manner with a peak during the early secretory phase of the menstrual cycle. Furthermore, the release of cytochrome c was seen in the early secretory phase. However, expression of FLIP(S) was only observed during the menstrual cycle in normal endometrial tissue. We concluded that the main apoptotic signalling in both normal human endometrial tissue and HHUA cells exposed to anti-Fas mAb is the mitochondrial pathway via Bid degradation. Although the function of FLIP is still unknown on normal endometrial tissue, it may be regulated by FLIP(L) expression on HHUA cells derived from human endometrial carcinoma.
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PMID:Caspase cascade of Fas-mediated apoptosis in human normal endometrium and endometrial carcinoma cells. 1687 Sep 53

Protein kinase CK2 (CK2) is a serine/threonine kinase that participates in important cellular processes. We have recently demonstrated that CK2 plays a role in resistance to TRAIL/Fas-induced apoptosis in endometrial carcinoma (EC) by regulating FLIP. Here, we assessed the immunohistochemical expression of CK2beta in EC and checked its role in cell proliferation and anchorage-independent cell growth. CK2beta immunostaining was assessed in two tissue microarrays, one constructed from paraffin-embedded blocks of 95 ECs and another from 70 samples of normal endometrium. CK2beta expression was correlated with histological type; grade and stage; cell proliferation (Ki-67) and apoptotic index; immunostaining for cyclin D1, PTEN, AKT, beta-catenin, and FLIP. Moreover, the Ishikawa EC cell line was subjected to down-regulation of CK2 by shRNA. CK2beta expression was frequent in EC (nuclear, 100%; cytoplasmic, 87.5%). The staining was more intense in EC than in normal endometrium (P = 0.000), and statistically correlated with AKT, PTEN, beta-catenin, and FLIP. In EC, CK2beta expression correlated with cell proliferation. Knock-down of CK2beta blocked colony formation of EC in soft agar, and also resulted in decreased expression of cyclin D1 and ERK phosphorylation. The results confirm that CK2beta is widely expressed in EC, and suggest a role in cell proliferation and anchorage-independent cell growth.
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PMID:CK2beta is expressed in endometrial carcinoma and has a role in apoptosis resistance and cell proliferation. 1905 46

The Raf/MEK/extracellular signal-regulated kinase (ERK) pathway participates in many processes altered in development and progression of cancer in human beings such as proliferation, transformation, differentiation, and apoptosis. Kinase suppressor of Ras 1 (KSR1) can interact with various kinases of the Raf/MEK/extracellular signal-regulated kinase pathway to enhance its activation. The role of KSR1 in endometrial carcinogenesis was investigated. cDNA and tissue microarrays demonstrated that expression of KSR1 was up-regulated in endometrial carcinoma. Furthermore, inhibition of KSR1 expression by specific small hairpin RNA resulted in reduction of both proliferation and anchorage-independent cell growth properties of endometrial cancer cells. Because inhibition of apoptosis has a pivotal role in endometrial carcinogenesis, the effects of KSR1 in regulation of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis were investigated. KSR1 knock-down sensitized resistant endometrial cell lines to both TRAIL- and Fas-induced apoptosis. Sensitization to TRAIL and agonistic anti-Fas antibody was caused by down-regulation of FLIP (FLICE-inhibitory protein). Also investigated was the molecular mechanism by which KSR1 regulates FLIP protein levels. It was demonstrated that KSR1 small hairpin RNA did not affect FLIP transcription or degradation. Rather, FLIP down-regulation was caused by Fas-associated death domain protein-dependent inhibition of FLIP translation triggered after TRAIL stimulation in KSR1-silenced cells. Re-expression of heterologous KSR1 in cells with down-regulated endogenous KSR1 restored FLIP protein levels and TRAIL resistance. In conclusion, KSR1 regulates endometrial sensitivity to TRAIL by regulating FLIP levels.
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PMID:KSR1 is overexpressed in endometrial carcinoma and regulates proliferation and TRAIL-induced apoptosis by modulating FLIP levels. 2143 42

Histone deacetylase inhibitors such as Vorinostat display anti-neoplastic activity against a variety of solid tumors. Here, we have investigated the anti-tumoral activity of Vorinostat on endometrial cancer cells. We have found that Vorinostat caused cell growth arrest, loss of clonogenic growth and apoptosis of endometrial cancer cells. Vorinostat-induced the activation of caspase-8 and -9, the initiators caspases of the extrinsic and the intrinsic apoptotic pathways, respectively. Next, we investigated the role of the extrinsic pathway in apoptosis triggered by Vorinostat. We found that Vorinostat caused a dramatic decrease of FLIP mRNA and protein levels. However, overexpression of the long from of FLIP did not block Vorinostat-induced apoptosis. To further investigate the role of extrinsic apoptotic pathway in Vorinostat-induced apoptosis, we performed an shRNA-mediated knock-down of caspase-8. Surprisingly, downregulation of caspase-8 alone caused a marked decrease in clonogenic ability and reduced the growth of endometrial cancer xenografts in vivo, revealing that targeting caspase-8 may be an attractive target for anticancer therapy on endometrial tumors. Furthermore, combination of caspase-8 inhibition and Vorinostat treatment caused an enhancement of apoptotic cell death and a further decrease of clonogenic growth of endometrial cancer cells. More importantly, combination of Vorinostat and caspase-8 inhibition caused a nearly complete inhibition of tumor xenograft growth. Finally, we demonstrate that cell death triggered by Vorinostat alone or in combination with caspase-8 shRNAs was inhibited by the anti-apoptotic protein Bcl-XL. Our results suggest that combinatory therapies using Vorinostat treatment and caspase-8 inhibition can be an effective treatment for endometrial carcinomas.
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PMID:Combination of Vorinostat and caspase-8 inhibition exhibits high anti-tumoral activity on endometrial cancer cells. 2359 Aug 18